Abstract

This study was aimed at enhancing the antitumour ef®cacy of bleomycin by encapsulating it in temperature-sensitive liposomes and using it in combination with localized hyperthermia of tumours for targeted delivery. Large unilammelar vesicles (LUV) made of synthetic lipids (disteroyl phosphatidylcholine and dipalmitoyl phosphatidylcholine) showing gel-to-liquid phase transition at 41�C, were used to encapsulate bleomycin. Comparison of LUV when incubated in saline at various temperatures revealed that maximum drug release (80%) occurred at 42�C compared with less than 5% release at 37�C. Better stability during storage was also observed with thermosensitive bleomycin liposomes. When administered intravenously to C57BL=6J mice bearing melanoma B16F1 tumour at 10 mg kg ÿ1 dose, liposomal bleomycin in combination with hyperthermia (43�C, 30 min or 1 h) exhibited improved anticancer activity as evident by the enhanced volume doubling time and growth delay compared with animals treated with an equivalent dose of f ee bleomycin with or without hyperthermia. The results suggest that hyperthermia in combination with bleomycin encapsulated inM temperature sensitive liposomes may be a useful targeted drug delivery system for more effective management of melanoma B16F1.